👤 Päivi Heikkilä

Small dense low-density lipoprotein (sdLDL) is atherogenic and associated with atherosclerotic cardiovascular diseases (ASCVD). The aim of this study was to perform the prospective evaluation of sdLDL-c in new ASCVD over 18 years of follow up, and to compare the association of sdLDL-c and conventional lipids and apolipoproteins with ASCVD in the elderly. This prospective study included a total of 1770 subjects ≥ 64 years of age with an 18-year follow-up period. The determination of sdLDL-c was measured by a homogenous, selective enzymatic method. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined by enzymatic methods. Apolipoproteins, ApoA1 and ApoB, were analyzed by immunonephelometric methods. Low-density lipoprotein cholesterol (LDL-c) levels were calculated using the Friedewald formula. According to Pearson's correlation coefficients, sdLDL-c concentration was positively correlated with LDL-c, nonHDL-c, TC and ApoB concentrations. During follow up, sdLDL-c was significantly associated with new ASCVD in men aged 64-76 years in both unadjusted and adjusted Cox regression models. The adjusted hazard ratio (95 % CI) for sdLDL-c was 1.61 (1.13-2.28). No significant associations between sdLDL-c and ASCVD were observed in men aged 77-97 years, nor in women aged 64-79 or 80-100 years. Lipid and apolipoprotein concentrations of the elderly were high compared to the recommended target values. In addition, lipid and apolipoprotein baseline concentrations were not higher in the ASCVD group than in the control group. Our results indicated that sdLDL-c is as good a marker as ApoB and better than LDL-c. Show less

The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic β-cell proliferation. Altered expression of a neighboring gene, Show less

Fetal akinesia deformation sequence (FADS) and lethal multiple pterygium syndrome (LMPS) are clinically overlapping syndromes manifesting with reduced or absent fetal movement, arthrogryposis, and several anomalies during fetal life. The etiology of these syndromes is heterogeneous, and in many cases it remains unknown. In order to determine the genetic etiology of FADS in two fetuses with fetal akinesia, arthrogryposis, edema, and partial cleft palate, we utilized exome sequencing. Our investigations revealed a homozygous nonsense variant [c.1116C>A, p.(Cys372Ter)] in the SLC18A3 gene, which encodes for the vesicular acetylcholine transporter (VAChT) responsible for active transport of acetylcholine in the neuromuscular junction. This is the first description of a nonsense variant in the SLC18A3 gene, as only missense variants and whole gene deletions have been previously identified in patients. The previously detected SLC18A3 defects have been associated with congenital myasthenic syndromes, and therefore our findings extend the clinical spectrum of SLC18A3 defects to severe prenatal phenotypes. Our findings suggest that nonsense variants in SLC18A3 cause a more severe phenotype than missense variants and are in line with previous studies showing a lethal phenotype in VAChT knockout mice. Our results underline the importance of including SLC18A3 sequencing in the differential diagnostics of fetuses with arthrogryposis, FADS, or LMPS of unknown etiology. Show less